Apoptotic Cell Death and Oxidative Stress in Huntington

Abstract

Event Abstract Back to Event Apoptotic Cell Death and Oxidative Stress in Huntington I. L. Ferreira1, M. Nascimento1, M. Ribeiro1, S. Almeida1, S. M. Cardoso1, C. Januario1, C. R. Oliveira1 and Ana Cristina-Rego1* 1 University of Coimbra, Center for Neuroscience and Cell Biology, Portugal Huntington’s disease (HD) is a neurodegenerative autosomic dominant disorder, characterized by motor and psychiatric disturbances, mainly affecting GABAergic medium-spiny neurons of the neostriatum. The disease- causing mutation consists of an expanded CAG tract at the N-terminal of huntingtin. Mitochondrial dysfunction has been proposed as an important mechanism of cell death in HD, supporting the defects in energy metabolism observed in HD patients. Furthermore, several evidences suggest the involvement of apoptosis and the generation of reactive oxygen species in neuronal death in HD. The aim of this work was to elucidate the susceptibility to mitochondrial-dependent apoptosis and the occurrence of oxidative stress in HD by using human cybrid cell lines from HD patient (HD cybrids) or control (CTR cybrids)subjects. We evaluated the susceptibility of HD cybrids compared to CTR cybrids upon complex II inhibition in the presence of 3-NP, or in the presence of STS (a classic apoptotic inducer. HD cybrids did not exhibit significant changes in the activity of mitochondrial respiratory chain complexes I-IV. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. We observed increased DNA fragmentation and moderate increased caspase-3 activation in HD cybrids, compared to CTR cybrids, upon stimulation with 3-NP or STS. An increase in superoxide production in HD cybrids in response to 3-NP or STS treatment and an increase in hydroperoxide production in non- treated HD cybrids was also observed. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death with a predominant loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their increased susceptibility to mitochondrial-dependent apoptosis. Our data support an increased susceptibility of HD cybrids compared to CTR cybrids to mitochondrial-dependent apoptosis involving oxidative stress, which may underlie HD pathogenesis.Supported by III/BIO/49/2005, STARTER S-09 and POCI/SAU-NEU/57310/2004. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neurodegenerative Disorders Citation: Ferreira IL, Nascimento M, Ribeiro M, Almeida S, Cardoso SM, Januario C, Oliveira CR and Cristina-Rego A (2009). Apoptotic Cell Death and Oxidative Stress in Huntington. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.110 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Aug 2009; Published Online: 10 Aug 2009. * Correspondence: Ana Cristina-Rego, University of Coimbra, Center for Neuroscience and Cell Biology, Alicante, Portugal, a.cristina.rego@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers I. L Ferreira M. Nascimento M. Ribeiro S. Almeida S. M Cardoso C. Januario C. R Oliveira Ana Cristina-Rego Google I. L Ferreira M. Nascimento M. Ribeiro S. Almeida S. M Cardoso C. Januario C. R Oliveira Ana Cristina-Rego Google Scholar I. L Ferreira M. Nascimento M. Ribeiro S. Almeida S. M Cardoso C. Januario C. R Oliveira Ana Cristina-Rego PubMed I. L Ferreira M. Nascimento M. Ribeiro S. Almeida S. M Cardoso C. Januario C. R Oliveira Ana Cristina-Rego Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.